Publications by authors named "Gregory Ferenchak"
Article Synopsis
- - The study investigates why tyrosine kinase inhibitors (TKIs) are ineffective on quiescent hematopoietic stem cells (HSCs) in chronic myeloid leukemia (CML), revealing that these resistant cells rely on the suppression of the tumor suppressor protein PP2A rather than the BCR-ABL1 kinase activity.
- - CML quiescent HSCs exhibited increased BCR-ABL1 expression without its kinase activity, leading to the activation of a survival pathway involving JAK2 and β-catenin, which further inhibited PP2A.
- - Treatment with PP2A-activating drugs (PADs) significantly impaired the survival and self-renewal of these CML
As tyrosine kinase inhibitors (TKIs) fail to induce long-term response in blast crisis chronic myelogenous leukemia (CML-BC) and Philadelphia chromosome-positive (Ph(+)) acute lymphoblastic leukemia (ALL), novel therapies targeting leukemia-dysregulated pathways are necessary. Exportin-1 (XPO1), also known as chromosome maintenance protein 1, regulates cell growth and differentiation by controlling the nucleocytoplasmic trafficking of proteins and RNAs, some of which are aberrantly modulated in BCR-ABL1(+) leukemias. Using CD34(+) progenitors from CML, B-ALL, and healthy individuals, we found that XPO1 expression was markedly increased, mostly in a TKI-sensitive manner, in CML-BC and Ph(+) B-ALL.
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